Ischemic stroke remains a major unsolved medical problem. Improved treatment will likely await better understanding of the complex underlying pathophysiology. Animal experiments, which can control many of the variable parameters, seem best for clarification of the stroke process. We have developed an awake monkey model for stroke with a number of advantages. The confusing effects of anesthesia are eliminated. Major physiologic variables are monitored, including total local cerebral blood flow (CBF). Temporary occlusion of the middle cerebral artery is achieved with the animals awake in a restraining chair. The model has uncovered important CBF thresholds for paralysis and infarction. We propose to utilize this model for further studies of pathophysiology and stroke treatment. In particular, we will examine the relation of EEG and evoked responses to CBF thresholds. In addition we plan to use our model to evaluate several therapies, including mannitol, hyperbaric oxygenation, and nitroglycerin.